rs17761734

chr17-2205559-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017575.5(SMG6):c.2870-17044G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 152,044 control chromosomes in the GnomAD database, including 1,302 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.11 (1302 hom., cov: 31)
• Consequence: SMG6 NM_017575.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.382

Genes affected

SMG6 (HGNC:17809): (SMG6 nonsense mediated mRNA decay factor) This gene encodes a component of the telomerase ribonucleoprotein complex responsible for the replication and maintenance of chromosome ends. The encoded protein also plays a role in the nonsense-mediated mRNA decay (NMD) pathway, providing the endonuclease activity near the premature translation termination codon that is needed to initiate NMD. Alternatively spliced transcript variants encoding distinct protein isoforms have been described. [provided by RefSeq, Feb 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.164 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMG6	NM_017575.5	c.2870-17044G>A		intron_variant		ENST00000263073.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMG6	ENST00000263073.11	c.2870-17044G>A		intron_variant		1	NM_017575.5	P1

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16809 AN: 151926 Hom.: 1301 Cov.: 31

Gnomad AFR AF: 0.0284

Gnomad AMI AF: 0.0725

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.000771

Gnomad SAS AF: 0.0455

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.141

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.111 AC: 16809 AN: 152044 Hom.: 1302 Cov.: 31 AF XY: 0.108 AC XY: 8009 AN XY: 74314

Gnomad4 AFR AF: 0.0284

Gnomad4 AMR AF: 0.121

Gnomad4 ASJ AF: 0.190

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.0459

Gnomad4 FIN AF: 0.111

Gnomad4 NFE AF: 0.166

Gnomad4 OTH AF: 0.141

Alfa AF: 0.139 Hom.: 811

Bravo AF: 0.108

Asia WGS AF: 0.0210 AC: 74 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	3.4
Dann	Benign	0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs17761734; hg19: chr17-2108853;